Mitochondrial DNA (mtDNA) heteroplasmy is an almost universal
condition in humans. The proportion of heteroplasmic mtDNA mutations that is
heritable rather than accumulated during life has, however, remained almost unknown.
The main goal of this work was to investigate the contribution of germinal versus
somatic heteroplasmy, exploring its impact on health and aging. Blood samples from
101 individuals were previously used to generate full mtDNA sequences. Taking into
account the embryonic origin of the tissues and the heterogeneity of site specific
mutation rate of mtDNA robust criteria of heteroplasmy classification was applied. The
mtDNA regions encompassing the 28 heteroplasmic positions detected in blood
samples were sequenced in buccal epithelial samples as a reference from an alternative
tissue with different embryonic origin. Based on the proposed classification data
published by Li et al. (2015) was reanalyzed. Moreover, the predicted functional
impact of non-synonymous mutations was evaluated. Most of heteroplasmies detected
were germinal or somatic prior gastrulation and most of the somatic heteroplasmies
were present in a single tissue. Somatic heteroplasmies were mostly present in older
individuals, suggesting that they could be related to aging process. Three out of five non-synonymous mutations in heteroplasmy (all of them classified as germinal or
somatic prior gastrulation) occurred in highly conserved positions, presenting a
probability >60% of being deleterious. Although germinal heteroplasmies (or somatic
prior gastrulation) can contribute to the development of disease and to the aging
process, most of the heteroplasmies detected in both studies present a level of the
alternative allele frequency below 60%, likely not affecting fitness and escaping
selection.
Keywords: Age, Disposable soma theory, Embryonic origin, Germinal, Health,
Heteroplasmy, MtDNA, Mutation accumulation theory, Purifying selection,
Somatic.
